Biotechnology and Bioprocess Engineering 2024; 29(5): 792-805  
Recent advancements in flavonoid production through engineering microbial systems
Yunhee Hwang1 · Myung Hyun Noh2 · Gyoo Yeol Jung1,3
1 Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Korea
2 Center for Bio‑Based Chemistry, Korea Research Institute of Chemical Technology (KRICT), Ulsan 44429, Korea
3 School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 37673, Korea
Correspondence to: ✉ Myung Hyun Noh
mhnoh@krict.re.kr
✉ Gyoo Yeol Jung
gyjung@postech.ac.kr
Received: April 15, 2024; Revised: June 15, 2024; Accepted: June 19, 2024; Published online: June 27, 2024.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Flavonoids are a class of polyphenolic compounds found in plants that offer extensive health benefits and have applications in the pharmaceutical, cosmetic, and food industries. Currently, flavonoid production largely depends on plant extraction methods, which face limitations owing to low yields and seasonal and environmental impacts. To address these issues, the potential of microbial fermentation, which leverages advances in metabolic engineering and genetic tools, has been discussed as an innovative alternative to overcome these challenges, thus offering an environmentally friendly and sustainable approach to flavonoid production. However, the integration of complex biosynthesis pathways into microbial systems presents challenges such as the inefficient expression of plant-derived genes, metabolic conflicts, and toxicity or feedback inhibition by accumulated flavonoids within the microbial cells. This comprehensive review highlights recent advancements in engineering strategies to address these challenges, focusing on biotransformation, single-strain fermentation, and co-culture systems, each with its own unique characteristics and potential for optimizing flavonoid production in a cost-effective and scalable manner.
Keywords: Flavonoid · Protein engineering · Pathway optimization · Co-culture

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